title: Microdeletion 5q14.3 and anomalies of brain development.
abstract: 5q14.3 deletions spanning and flanking MEF2C as well as intragenic MEF2C mutations have recently been described as a cause of severe intellectual disability, epilepsy, and muscular hypotonia, with variable brain and other anomalies. With an increasing number of patients described, the clinical presentation of the patients appears to be relatively uniform, however the structural brain phenotypes described are variable. We describe two unrelated patients with overlapping de novo interstitial deletions of 4.1 and 1.9 Mb, including MEF2C in 5q14.3, one of whom had a complex brain malformation which could be best described as microcephaly with simplified gyral pattern (MSG). Expression analysis in both patients confirmed haploinsufficiency for MEF2C, decreased MECP2 expression and increased C3ORF58 (DIA1) expression, which is a new finding. A detailed analysis of brain and white matter abnormalities reported in patients with 5q14.3 deletion syndrome to date revealed a greater number of reported abnormalities in patients with deletions not including MEF2C than those with deletions or mutations directly affecting MEF2C. Screening an additional 43 patients with malformations of cerebral cortical development (MCD) for mutations in MEF2C and/or deletions in 5q14.3q15, did not detect any additional mutations, allowing us to conclude that 5q14.3 deletion syndrome is a rare cause of microcephaly with simplified gyral pattern.
authors.affiliation: Institute of Human Genetics, Albert-Ludwigs University Medical Centre Freiburg, Freiburg, Germany.
authors.forename: Alrun
authors.initials: A
authors.lastname: Hotz
authors.forename: Yorck
authors.initials: Y
authors.lastname: Hellenbroich
authors.forename: Jürgen
authors.initials: J
authors.lastname: Sperner
authors.forename: Michaela
authors.initials: M
authors.lastname: Linder-Lucht
authors.forename: Uta
authors.initials: U
authors.lastname: Tacke
authors.forename: Caren
authors.initials: C
authors.lastname: Walter
authors.forename: Almuth
authors.initials: A
authors.lastname: Caliebe
authors.forename: Inga
authors.initials: I
authors.lastname: Nagel
authors.forename: Dawn E
authors.initials: DE
authors.lastname: Saunders
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wolff
authors.forename: Peter
authors.initials: P
authors.lastname: Martin
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Morris-Rosendahl
mesh_terms: D001921:Brain / Q000473:pathology; D002675:Child, Preschool; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5; D055028:Comparative Genomic Hybridization; D019066:Facies; D006801:Humans; D064326:MEF2 Transcription Factors / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D054220:Malformations of Cortical Development / Q000175:diagnosis / Q000235:genetics*
chemical_list: D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human
keywords: MEF2C; cortical malformation; epilepsy; intellectual disability; microdeletion 5q14.3 syndrome